Flashcards in multiplesclerosisFC Deck (15):
What is mulitple sclerosis?
Autoimmune, environmental / genetic etiology, chronic inflammation of CNS, myelin loss - plague and lesions form, early axonal loss, results in periodic loss of neurologic function -> progressive disability. 3:1 women, 20-40 y.o.
What are the three components of multiple sclerosis immunopathogenesis?
Inflammation - immune mediated, faciliated by the entry of autoreactive T cells and demyelinating antibodies from the blood stream into the CNS. Demyelination - immune/AB mediated, CD4+ cells and activated B cells, Axonal injury and loss - first 2 lead to axonal injury and brain atrophy
How does inflammation occur in the CNS to start MS?
CSF usually sterile, sentential T-cells entry if something gets recognized, leads to breakdown of BBB, antibody and complement system -> inflame -> attacks oligodendrocytes which make myelin and myelin.
How does MS get diagnosed?
difficult to diagnose, need two neurological attacks at separate times, need evidence of lesions on MRI
What are the symptoms of MS?
Physical - sensory symptoms, weakness, spasticity, paralysis, chronic pain, fatigue, paroxysmal symptoms, bladder/bowel/sexual dysfxn. Cognitive - information / learning, executive, solving, attention span. Psychologic - depression, personality, mood changes
What are the therapy goals of MS? Tx Options?
Slow the progression of disease, reduce relapse rate, reduce CNS lesion burden, slow accumulation of disability, reduce brain atrophy, improve QoL. Options - disease modifying therapy, treat symptoms medications, exacerbations - steroids
What are the FDA approved MS therapies?
Rebif B-1a 22mcg SQ TIW, Avonex B-1a 30 mcg IM QW, Betaseron / Extavia B-1b 250 mcg SQ QOD, Copaxone Glatiramer 20 mg SQ QD, Tysabri Natalizumab 300 mg Qmonth, Novantrone Mitoxantrone (leukemia) 12 mg/m2 IV q3months, Aubagio teriflunomide 7 mg QD, Gilenya Fingolimod (Cardiac deaths) 10 mg PO QD.
What is the treatment algorithm for MS?
Start with FDA approved medication, for breakthrough use corticosteroids prn, if continued break through new immunomodulator / maintenance + roids / Oral or IV immunosuppressant
What are the side effects of IFN-Betas and Glatiramer?
Betas - 24hr of feeling like a truck hit you, flu like symptoms (NSAIDs), muscle ache, fever. GA - immediate systemic post injection reactions (anxiety like attack), CP, injxn site (ice / EMLA), lipoatrophy
What is the "best" MS drug (according to lecturer)? Why is it special? ADRs?
Tysabri - natalizumab - mab to alpha 4 integrin (blocks entry into CNS), decreased immunogenicity and increased HL. Increased risk of PML (progressive multifocal leukoencephalopathy) iPledge like system in place,
What is Gilenya? MoA? Issues?
analogue to sphingosine - prevents exit of activated T-Cells from lymphocytes, problem is they are everywhere. Also has 2 peaks which have highest risk of death, cannot have monitors on patient whole time. need EKG
What is Teriflunomide?
active metabolie of leflunomide, inhibs rapidly dividing lymphocytes, only oral MS drug
What is the most common symptom experienced with MS? 2nd most?
Bladder / Bowel problems - hyperexcitable bladder - pulses with urge, but rarely large volume (need to relax bladder). Fatigue (2nd) - tx with amantadine, modafinil, methylphenidate, adderall, bupropion
What is the 3rd most common symptom with MS?
Spasticity - demyelination in nerves that regulate muscle tone, stiffness. Tx - tx problems that increase spasticity (infxn, pain, skin breakdown), stretching, aids, medication (baclofen, tizanidine, diazepam)